Effects of Switching From Racemic Methadone to R-methadone on QTc Intervals

NCT04254731 | Active Not Recruiting Phase 4

• 1 other identifier: 2012/793 REK
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 3

Brief Summary

Effects of switching from racemic methadone to R-methadone on serum methadone concentrations and QTc intervals

Conditions

Adverse Drug Effect; Drug Effect; Heart Arrhythmia

Keywords

Racemic methadone; R-methadone; QTc interval; Methadone maintenance treatment patients

Outcome Measures

Primary Outcomes (4)

• Effects of switching from racemic methadone to R-methadone on serum methadone concentrations.

  Ten patients stabilized on racemic methadone dose were switched to R-methadone and effects on serum methadone concentrations were studied. Methadone concentrations (nmol/L) were measured by validated high pressure liquid chromatography coupled to mass spectrometry detection (LC-MSMS).

  Time frame of each patient form inclusion to end study was 35-40 days.

• Effects of switching from racemic methadone to R-methadone on QTc interval

  In ten patients QTc intervals were recorded on racemic methadone treatment at Cmin and Cmax of methadone drug concentrations and likewise after the shift to R-methadone. QT intervals (ms) on ECG were recorded automatically and read manually by experienced cardiologists.

  Time frame of each patient form inclusion to end study was 35-40 days.

• Effects of switching from racemic methadone to R-methadone on opioid withdrawal symptoms (OWS)

  Ten patients: each patients had OWS recorded on racemic and R-methadone treatment using OWS.

  Time frame of each patient form inclusion to end study was 35-40 days.

• Effects of switching from racemic methadone to R-methadone, stability of serum electrolytes (Ca, Mg, K) in patients

  Ten patients: samples for serum electrolytes were collected before and after switch to R-methadone. Measured by routine analysis at Cobas 8000 (unit mmol/L)

  Time frame of each patient form inclusion to end study was 35-40 days.

Study Arms (1)

Cross over study before and after drug switch

OTHER

Stabilized on racemic methadone dose, switched to R-methadone of half racemic methadone dose. Cross over study, own control

Drug: Same individuals treated with racemic methadone and switched to levomethadone (R-methadone)

Interventions

Same individuals treated with racemic methadone and switched to levomethadone (R-methadone) DRUG

Also known as: Drugs provided from the pharmaceutical company called DnePharma AS (Den norske Eterfabrikk ( DnE), address Karihaugen 22, Oslo, Norway, drug delivered to patient from home nurse or pharmacy

Cross over study before and after drug switch

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Stabilized on daily methadone dose
• Not using other drugs of abuse
• Older than 18 years
• Can sign and understand a written Consent

You may not qualify if:

• Can not cooperate regarding observed daily drug intake
• Serious psychiatric disease
• Untreated serious somatic disease
• Pregnancy

Sponsors & Collaborators

• Oslo University Hospital: lead

Study Sites (3)

Department of Pharmacology , Oslo University Hospital

Oslo, 0424, Norway

Location

Department of Pharmacology and Department of Substance Use Disorder, Oslo University Hospital

Oslo, 0424, Norway

Location

Department of Substance Use Disorder, Oslo University Hospital

Oslo, 0424, Norway

Location

Related Publications (1)

• Havig SM, Berg-Pedersen RM, Krabseth HM, Muller LD, Haugaa K, Zare HK, Gjesdal K, Krajci P, Opdal MS. Effect on QTc interval by switching from methadone to equipotent R-methadone dose in methadone maintenance treatment patients. Basic Clin Pharmacol Toxicol. 2024 Apr;134(4):519-530. doi: 10.1111/bcpt.13982. Epub 2024 Feb 3.

  PMID: 38308508 BACKGROUND

Related Links

• abstract from EACPT 2019, see abstract 1168

MeSH Terms

Conditions

Drug-Related Side Effects and Adverse Reactions; Arrhythmias, Cardiac

Interventions

Dosage Forms

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations; Technology, Pharmaceutical; Investigative Techniques

Study Officials

• Mimi Stokke S Opdal, MD, PhD

  Oslo University Hospital and University of Oslo

  STUDY DIRECTOR

• Peter Krajci, MD, PhD

  Oslo University Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Consultant and Associate Professor of Clinical Pharmacology

Model Details: Patients included were stabilized on per os methadone maintenance treatment and had automatically ECG recorded QTc interval greater or equal to 450 ms. The patients were switched to pure R-methadone per os (half dose of the racemic methadone used). Doses, serum drug concentrations, QTc-time were recorded before and after drug switch. Serum-electrolytes (Mg, K, Ca) and opioid withdrawal symptom scale (OWS) were also measured and scored before and after drug switch.

Study Record Dates

• First Submitted: January 6, 2020
• First Posted: February 5, 2020
• Study Start: May 7, 2015
• Primary Completion: June 27, 2018
• Study Completion: July 30, 2024
• Last Updated: April 3, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Protocol in Norwegian attached
• Access Criteria: IPD proving the results of the different outcome measures will be shared, see above

Locations

NO (3)